High-Intensity Blue Light (450-460 nm) Phototherapy for Pseudomonas aeruginosa-Infected Wounds.

Background: Nosocomial wound infection with Pseudomonas aeruginosa (PA) is a serious complication often responsible for the septic mortality of burn patients. Objective: High-intensity antimicrobial blue light (aBL) treatment may represent an alternative therapy for PA infections and will be investigated in this study. Methods: Antibacterial effects of a light-emitting diode array (450-460 nm; 300 mW/cm2; 15/30 min; 270/540 J/cm2) against PA were determined by suspension assay, biofilm assay, and a human skin wound model and compared with 15-min topically applied 3% citric acid (CA) and wound irrigation solution (Prontosan®; PRT). Results: aBL reduced the bacterial number [2.51-3.56 log10 colony-forming unit (CFU)/mL], whereas PRT or CA treatment achieved a 4.64 or 6.60 log10 CFU/mL reduction in suspension assays. aBL reduced biofilm formation by 60-66%. PRT or CA treatment showed reductions by 25% or 13%. Here, aBL reduced bacterial number in biofilms (1.30-1.64 log10 CFU), but to a lower extend than PRT (2.41 log10 CFU) or CA (2.48 log10 CFU). In the wound skin model, aBL (2.21-2.33 log10 CFU) showed a bacterial reduction of the same magnitude as PRT (2.26 log10 CFU) and CA (2.30 log10 CFU). Conclusions: aBL showed a significant antibacterial efficacy against PA and biofilm formation in a short time. However, a clinical application of aBL in wound therapy requires effective active skin cooling and eye protection, which in turn may limit clinical implementation.

High-Intensity Blue Light (450-460 nm) Phototherapy for Pseudomonas aeruginosa-Infected Wounds.

Background: Nosocomial wound infection with Pseudomonas aeruginosa (PA) is a serious complication often responsible for septic mortality of burn patients. High-intensity antimicrobial blue light (aBL) treatment may represent an alternative therapy for PA infections. Methods: Antibacterial effects of an light-emitting diode (LED) array (450-460 nm; 300 mW/cm2; 15/30 min; 270/540J/cm2) against PA were determined by suspension assay, biofilm assay, and a human skin wound model and compared with 15-min topically applied 3% citric acid (CA) and wound irrigation solution (Prontosan®; PRT). Results: The aBL reduced the bacterial number (2.51-3.56 log10 CFU/mL), whereas PRT or CA treatment achieved a 4.64 or 6.60 log10 CFU/mL reduction in suspension assays. The aBL reduced biofilm formation by 60%-66%. PRT or CA treatment showed reductions by 25% or 13%. In this study, aBL reduced bacterial number in biofilms (1.30-1.64 log10 CFU), but to a lower extent than PRT (2.41 log10 CFU) or CA (2.48 log10 CFU). In the wound skin model, aBL (2.21-2.33 log10 CFU) showed a bacterial reduction of the same magnitude as PRT (2.26 log10 CFU) and CA (2.30 log10 CFU). Conclusions: The aBL showed a significant antibacterial efficacy against PA and biofilm formation in a short time. However, a clinical application of aBL in wound therapy requires effective active skin cooling and eye protection, which in turn may limit clinical implementation.

Experimental evidence for Parthanatos-like mode of cell death of heat-damaged human skin fibroblasts in a cell culture-based in vitro burn model.

The cellular mechanisms of burn conversion of heat damaged tissue are center of many studies. Even if the molecular mechanisms of heat-induced cell death are controversially discussed in the current literature, it is widely accepted that caspase-mediated apoptosis plays a central role. In the current study we wanted to develop further information on the nature of the mechanism of heat-induced cell death of fibroblasts in vitro. We found that heating of human fibroblast cultures (a 10 s rise from 37 °C to 67 °C followed by a 13 s cool down to 37 °C) resulted in the death of about 50% of the cells. However, the increase in cell death started with a delay, about one hour after exposure to heat, and reached the maximum after about five hours. The lack of clear evidence for an active involvement of effector caspase in the observed cell death mechanism and the lack of observation of the occurrence of hypodiploid nuclei contradict heat-induced cell death by caspase-mediated apoptosis. Moreover, a dominant heat-induced increase in PARP1 protein expression, which correlated with a time-delayed ATP synthesis inhibition, appearance of double-strand breaks and secondary necrosis, indicate a different type of cell death than apoptosis. Indeed, increased translocation of Apoptosis Inducing Factor (AIF) and Macrophage Migration Inhibitory Factor (MIF) into cell nuclei, which correlates with the mentioned enhanced PARP1 protein expression, indicate PARP1-induced, AIF-mediated and MIF-activated cell death. With regard to the molecular actors involved, the cellular processes and temporal sequences, the mode of cell death observed in our model is very similar to the cell death mechanism via Parthanatos described in the literature.

Which Moisturizer to Use in Scar Therapy after Burn Injuries? A Subjective and Objective Skin and Scar Evaluation after Topical Treatment with Dexpanthenol, Aloe Vera, and Plant Oil.

Background and Objectives: Good scar management in burn care is essential. Nevertheless, there are no consistent recommendations regarding moisturizers for scar management. Our aim was to investigate and compare the effects of commonly used products on normal skin and burn scars. Materials and Methods: A total of 30 skin-healthy (control group) and 12 patients with burn scars were included in this study. For an intraindividual comparison, each participant received creams consisting of dexpanthenol (P), aloe vera (A), and a natural plant oil (O) with instructions to apply them daily to a previously defined area for at least 28 days. Objective scar evaluation was performed with Visioscan®; Tewameter®; Cutometer®, and the Oxygen To See® device. Subjective evaluation was performed with an "application" questionnaire, the Patient and Observer Scar Assessment Scale (POSAS), and with the "best of three" questionnaire. Results: After (A) a high trend of amelioration of +30%, TEWL was detected on the scar area. Blood flow increased slightly on healthy skin areas after (A) application to +104%. The application of (A) on healthy skin demonstrated a positive effect on the parameters of scaliness (+22%, p < 0.001), softness (+14%, p = 0.046), roughness R1 (+16%, p < 0.001) and R2 (+17%, p = 0.000), volume (+22%, p < 0.001), and surface area (+7%, p < 0.001) within the control group. After (P), a significant improvement of the baseline firmness parameter of +14.7% was detected (p = 0.007). (P) also showed a beneficial effect on the parameters of R1 (+7%, p = 0.003), R2 (+6%, p = 0.001), and volume (+17%, p = 0.001). (O) lead to a statistically significant improvement of volume (+15%, p = 0.009). Overall, most study participants stated (A) to be the "best of three". Conclusions: (A) performed statistically best, and is a well-tolerated moisturizing product. However, further quantitative studies are needed to provide statistically significant clarification for uniform recommendations for scar therapy.

Phototherapy of Pseudomonas aeruginosa-Infected Wounds: Preclinical Evaluation of Antimicrobial Blue Light (450-460 nm) Using In Vitro Assays and a Human Wound Skin Model.

Objective: To determine effective treatment strategies against bacterial infections of burn wounds with Pseudomonas aeruginosa, we tested different treatment regimens with antibacterial blue light (BL). Background: Infections of burn wounds are serious complications and require effective and pathogen-specific therapy. Hereby, infections caused by P. aeruginosa pose a particular challenge in clinical practice due to its resistance to many antibiotics and topical antiseptics. Methods: LED-based light sources (450-460 nm) with different intensities and treatment times were used. Antibacterial effects against P. aeruginosa were determined by colony-forming unit (CFU) assays, human skin wound models, and fluorescence imaging. Results: In suspension assays, BL (2 h, 40 mW/cm2, 288 J/cm2) reduced bacterial number (>5 log10 CFU/mL). Applying 144 J/cm2, using 40 mW/cm2 for 1 h was more effective (>4 log10 CFU) than using 20 mW/cm2 for 2 h (>1.5 log10 CFU). BL with low irradiance (24 h, 3.5 mW/cm2, 300 J/cm2) only revealed bacterial reduction in thin bacteria-containing medium layers. In infected in vitro skin wounds only BL irradiation (2 h, 40 mW/cm2, 288 J/cm2) exerted a significant antimicrobial efficacy (2.94 log10 CFU/mL). Conclusions: BL treatment may be an effective therapy for P. aeruginosa-infected wounds to avoid radical surgical debridement. However, a significant antibacterial efficacy can only be achieved with higher irradiances and longer treatment times (min. 40 mW/cm2; >1 h), which cannot be easily integrated into regular clinical treatment protocols, for example, during a dressing change. Further studies are necessary to establish BL therapy for infected burns among tissue compatibility and interactions with previous therapeutic agents.

Utility of Intravenous Curcumin Nanodelivery Systems for Improving In Vivo Pharmacokinetics and Anticancer Pharmacodynamics.

Curcumin nanoformulations for intravenous injection have been developed to offset poor absorption, biotransformation, degradation, and excessive clearance associated with parenteral delivery. This review investigates (1) whether intravenous nanoformulations improve curcumin pharmacokinetics (PK) and (2) whether improved PK yields greater therapeutic efficacy. Standard PK parameters (measured maximum concentration [Cmax], area under the curve [AUC], distribution volume [Vd], and clearance [CL]) of intravenously administered free curcumin in mice and rats were sourced from literature and compared to curcumin formulated in nanoparticles, micelles, and liposomes. The studies that also featured analysis of pharmacodynamics (PD) in murine cancer models were used to determine whether improved PK of nanoencapsulated curcumin resulted in improved PD. The distribution and clearance of free and nanoformulated curcumin were very fast, typically accounting for >80% curcumin elimination from plasma within 60 min. Case-matched analysis demonstrated that curcumin nanoencapsulation generally improved curcumin PK in terms of measured Cmax (n = 27) and AUC (n = 33), and to a lesser extent Vd and CL. However, when the data were unpaired and clustered for comparative analysis, only 5 out of the 12 analyzed nanoformulations maintained a higher relative curcumin concentration in plasma over time compared to free curcumin. Quantitative analysis of the mean plasma concentration of free curcumin versus nanoformulated curcumin did not reveal an overall marked improvement in curcumin PK. No correlation was found between PK and PD, suggesting that augmentation of the systemic presence of curcumin does not necessarily lead to greater therapeutic efficacy.

Lyophilization stabilizes clinical-stage core-crosslinked polymeric micelles to overcome cold chain supply challenges.

BACKGROUND: CriPec technology enables the generation of drug-entrapped biodegradable core-crosslinked polymeric micelles (CCPM) with high drug loading capacity, tailorable size, and drug release kinetics. Docetaxel (DTX)-entrapped CCPM, also referred to as CPC634, have demonstrated favorable pharmacokinetics, tolerability, and enhanced tumor uptake in patients. Clinical efficacy evaluation is ongoing. CPC634 is currently stored (shelf life > 5 years) and shipped as a frozen aqueous dispersion at temperatures below -60°C, in order to prevent premature release of DTX and hydrolysis of the core-crosslinks. Consequently, like other aqueous nanomedicine formulations, CPC634 relies on cold chain supply, which is unfavorable for commercialization. Lyophilization can help to bypass this issue. METHODS AND RESULTS: Freeze-drying methodology for CCPM was developed by employing CPC634 as a model formulation, and sucrose and trehalose as cryoprotectants. We studied the residual moisture content and reconstitution behavior of the CPC634 freeze-dried cake, as well as the size, polydispersity index, morphology, drug retention, and release kinetics of reconstituted CPC634. Subsequently, the freeze-drying methodology was validated in an industrial setting, yielding a CPC634 freeze-dried cake with a moisture content of less than 0.1 wt%. It was found that trehalose-cryoprotected CPC634 could be rapidly reconstituted in less than 5 min at room temperature. Critical quality attributes such as size, morphology, drug retention, and release kinetics of trehalose-cryoprotected freeze-dried CPC634 upon reconstitution were identical to those of non-freeze-dried CPC634. CONCLUSION: Our findings provide proof-of-concept for the lyophilization of drug-containing CCPM and our methodology is readily translatable to large-scale manufacturing for future commercialization.

In Vitro and In Vivo Studies on HPMA-Based Polymeric Micelles Loaded with Curcumin.

Curcumin-loaded polymeric micelles composed of poly(ethylene glycol)-b-poly(N-2-benzoyloxypropyl methacrylamide) (mPEG-b-p(HPMA-Bz)) were prepared to solubilize and improve the pharmacokinetics of curcumin. Curcumin-loaded micelles were prepared by a nanoprecipitation method using mPEG5kDa-b-p(HPMA-Bz) copolymers with varying molecular weight of the hydrophobic block (5.2, 10.0, and 17.1 kDa). At equal curcumin loading, micelles composed of mPEG5kDa-b-p(HPMA-Bz)17.1kDa showed better curcumin retention in both phosphate-buffered saline (PBS) and plasma at 37 °C than micelles based on block copolymers with smaller hydrophobic blocks. No change in micelle size was observed during 24 h incubation in plasma using asymmetrical flow field-flow fractionation (AF4), attesting to particle stability. However, 22-49% of the curcumin loading was released from the micelles during 24 h from formulations with the highest to the lowest molecular weight p(HPMA-Bz), respectively, in plasma. AF4 analysis further showed that the released curcumin was subsequently solubilized by albumin. In vitro analyses revealed that the curcumin-loaded mPEG5kDa-b-p(HPMA-Bz)17.1kDa micelles were internalized by different types of cancer cells, resulting in curcumin-induced cell death. Intravenously administered curcumin-loaded, Cy7-labeled mPEG5kDa-b-p(HPMA-Bz)17.1kDa micelles in mice at 50 mg curcumin/kg showed a long circulation half-life for the micelles (t1/2 = 42 h), in line with the AF4 results. In contrast, the circulation time of curcumin was considerably shorter than that of the micelles (t1/2α = 0.11, t1/2ß = 2.5 h) but ∼5 times longer than has been reported for free curcumin (t1/2α = 0.02 h). The faster clearance of curcumin in vivo compared to in vitro studies can be attributed to the interaction of curcumin with blood cells. Despite the excellent solubilizing effect of these micelles, no cytostatic effect was achieved in neuroblastoma-bearing mice, possibly because of the low sensitivity of the Neuro2A cells to curcumin.

Ultrasonic-assisted production of zero-valent iron-decorated graphene oxide/activated carbon nanocomposites: Chemical transformation and structural evolution.

Nanotechnology has revolutionized many fields and produced nanostructures are promising materials for different industries. Nanoadsorbents as an emerging class of nanostructures can have potential applications for the separation and removal of both hazardous materials (such as heavy metals from water) and useful ingredients (such as vitamins and natural pigments from food wastes). The present study introduces a novel nanoadsorbent based on the ternary combination of zero valent iron/graphene oxide/active carbon (nZVI/GO-AC) with different formulations and using ultrasonication for improved physical properties. The nanocomposites were prepared by sodium borohydride reduction of graphene oxide, active carbon and ferrous sulfate under a nitrogen atmosphere and ultrasonication. Characterization of the developed nanocomposites was done by instrumental techniques, such as FTIR, VSM, FE-SEM, XRD, EDS, AFM and Raman analysis. The results indicated that the size of particles was 50 nm in the blank sample; however, when GO entered the composition, the particle size switched to <10 nm (either with or without ultrasonication). Also, the crystallinity of the ultrasound-assisted prepared nanocomposites enhanced by rapid nucleation in this method. Interestingly, the nanocomposites were superparamagnetic at ambient temperature and were separated by an external magnetic field. Altogether, at lower concentrations of GO in comparison to active carbon, the space between the GO sheets was higher and thus, there was more space for the accommodation of nZVI, which raises the rate of adsorbance. The immobilization process of nZVI on the composite platform improves the stability of the nZVI, whereas graphene coupling accelerates the transfer of electrons in nZVI and hinders the surface passivation of nZVI, resulting in the adsorption of target compounds.

Systematic evaluation of design features enables efficient selection of Π electron-stabilized polymeric micelles.

Polymeric micelles (PM) based on poly(ethylene glycol)-b-poly(N-2-benzoyloxypropyl methacrylamide) (mPEG-b-p(HPMA-Bz)) loaded with paclitaxel (PTX-PM) have shown promising results in overcoming the suboptimal efficacy/toxicity profile of paclitaxel. To get insight into the stability of PTX-PM formulations upon storage and to optimize their in vivo tumor-targeted drug delivery properties, we set out to identify a lead PTX-PM formulation with the optimal polymer composition. To this end, PM based on four different mPEG5k-b-p(HPMA-Bz) block copolymers with varying molecular weight of the hydrophobic block (17-3 kDa) were loaded with different amounts of PTX. The hydrodynamic diameter was 52 ± 1 nm for PM prepared using polymers with longer hydrophobic blocks (mPEG5k-b-p(HPMA-Bz)17k and mPEG5k-b-p(HPMA-Bz)10k) and 39 ± 1 nm for PM composed of polymers with shorter hydrophobic blocks (mPEG5k-b-p(HPMA-Bz)5k and mPEG5k-b-p(HPMA-Bz)3k). The best storage stability and the slowest PTX release was observed for PM with larger hydrophobic blocks. On the other hand, smaller sized PM of shorter mPEG5k-b-p(HPMA-Bz)5k showed a better tumor penetration in 3D spheroids. Considering better drug retention capacity of the mPEG5k-b-p(HPMA-Bz)17k and smaller size of the mPEG5k-b-p(HPMA-Bz)5k as two desirable design features, we argue that PM based on these two polymers are the lead candidates for further in vivo studies.

Ultrasound-guided lymphangiography and interventional embolization of chylous leaks following esophagectomy.

OBJECTIVES: Postoperative chylothorax is a serious complication after transthoracic esophagectomy, and is associated with major morbidity due to dehydration and malnutrition. For patients with high-output fistula, re-thoracotomy with ligation of the thoracic duct is the treatment of choice. Radiologic interventional management is an innovative procedure that has the potential to replace surgery in the treatment algorithm. METHODS: Four patients with high-output chylous leaks following esophagectomy are presented. Ultrasound-guided lymphangiography with embolization of the thoracic duct and/or disruption of the cisterna chyli was performed to occlude the leakage site. Radiologic interventions and procedure-related outcomes are described in detail. RESULTS: In all four patients, ultrasound-guided lymphangiography of the groin with injection of Lipiodol was able to detect and visualize the leakage site in the lower mediastinum. In three patients, the leak could be successfully occluded by Lipiodol embolization. In one patient, embolization failed and the disruption technique was successfully performed. No procedure-related complications were observed. CONCLUSIONS: In case of a postoperative chylothorax, radiologic intervention is feasible and safe. The procedure is indicated for high-output chylous fistulas after esophagectomy, and should be applied early after the diagnosis of this postoperative complication.

Development of ternary nanoadsorbent composites of graphene oxide, activated carbon, and zero-valent iron nanoparticles for food applications.

In this study, a ternary nanocomposite comprising graphene oxide and carbon loaded with zero-valent iron nanoparticles was developed as a promising nanoadsorbent, especially for polyphenols available in food industry by-products. The fabricated nanoadsorbents were characterized in terms of structural, morphological, and chemical attributes. Zero-valent iron nanoparticles (nZVI) were produced by a modified method leading to the formation of nanoparticles below 50 nm. Also, active carbon was transformed to a needle-like shape instead of its native shape so that the active surface area was drastically increased which favors the higher adsorption process. Moreover, the space between graphene oxide sheets was enhanced by ultrasonication so that more active carbon and nZVIs could be oriented between these sheets. Finally, the FTIR and Raman data demonstrated the formation of O-H stretching groups and a D/G value of 0.85 corresponding to the maintenance of a desired structure of the graphene oxide sheets, respectively. To summarize, the developed nanocomposites can be employed as a promising tool for the adsorbance of food and beverage industry by-products, especially polyphenols.

Scale-Up of the Manufacturing Process To Produce Docetaxel-Loaded mPEG-b-p(HPMA-Bz) Block Copolymer Micelles for Pharmaceutical Applications.

An efficient, scalable, and good manufacturing practice (GMP) compatible process was developed for the production of docetaxel-loaded poly(ethylene glycol)-b-poly(N-2-benzoyloxypropyl methacrylamide) (mPEG-b-p(HPMA-Bz)) micelles. First, the synthesis of the mPEG-b-p(HPMA-Bz) block copolymer was optimized through step-by-step investigation of the batch synthesis procedures. This resulted in the production of 1 kg of mPEG-b-p(HPMA-Bz) block copolymer with a 5 kDa PEG block and an overall molecular weight of 22.5 kDa. Second, the reproducibility and scalability of micelle formation was investigated for both batch and continuous flow setups by assessing critical process parameters. This resulted in the development of a new and highly efficient continuous flow process, which led to the production of 100 mL of unloaded micelles with a size of 55 nm. Finally, the loading of the micelles with the anticancer drug docetaxel was successfully fine-tuned to obtain precise control on the loaded micelle characteristics. As a result, 100 mL of docetaxel-loaded micelles (20 mg/mL polymer and 5 mg/mL docetaxel in the feed) with a size of 55 nm, an encapsulation efficiency of 65%, a loading capacity of 14%, and stable for at least 2 months in water at room temperature were produced with the newly developed continuous flow process. In conclusion, this study paves the way for efficient and robust large-scale production of docetaxel-loaded micelles with high encapsulation efficiencies and stability, which is crucial for their applicability as a clinically relevant drug delivery platform.

Regulation of in vivo behavior of TAT-modified liposome by associated protein corona and avidity to tumor cells.

INTRODUCTION: PEGylated liposomes are widely used and studied as carriers for chemotherapeutics. While pharmacokinetics of the encapsulated drug is drastically altered resulting in favorable circulation time, improved tumor accumulation, and better manageable or reduced side effects, therapeutic efficacy has been disappointing. Major drawbacks are a failure to reach the tumor cell, limited penetration depth, and impaired uptake by tumor cells. MATERIALS AND METHODS: Here, we study the implication of HIV-1 transactivator of transcription (TAT)-derived peptides inserted on PEGylated liposomal doxorubicin (PLD) and followed in vitro and in vivo fate. PLDs were installed with 25-400 TAT peptides per liposome without an effect on PLD stability. RESULTS: While TAT peptides facilitate active endocytosis of the carriers, we observed that these peptides did not promote endosomal escape or enhanced intracellular availability of doxorubicin. Interestingly, incorporation of TAT peptides did not change pharmacokinetics or biodistribution, which we found to result from a dysopsonization of the TAT-modified liposomes by serum proteins. A protein corona (PC) on TAT peptide-modified PLDs shields the active moieties and effectively reduces clearance of the TAT peptide containing nanoparticles. However, intratumoral activity was influenced by the number of TAT peptides present. The best antitumor efficacy was observed with a TAT peptide density of 100, while lower amounts showed results comparable to unmodified PLDs. At 200 TAT peptides, the preparation appeared to be least effective, which likely results from augmented interaction with tumor cells directly upon extravasation. CONCLUSION: We conclude that by optimizing TAT-modified PLDs, the occurring PC balances pharmacokinetics and tumor penetration through interference with avidity.

Effect of induced polyploidy on some biochemical parameters in Cannabis sativa L.

This study is aimed at testing the efficiency of colchicine on inducing polyploidy in Cannabis sativa L. and investigation of effects of polyploidy induction on some primary and secondary metabolites. Shoot tips were treated with three different concentrations of colchicine (0, 0.1, 0.2 % w/v) for 24 or 48 h. The biggest proportion of the almost coplanar tetraploids (43.33 %) and mixoploids (13.33 %) was obtained from the 24-h treatment in 0.2 and 0.1 % w/v, respectively. Colchicine with 0.2 % concentration and 48 h duration was more destructive than 24 h. The ploidy levels were screened with flow cytometry. The biochemical analyses showed that reducing sugars, soluble sugars, total protein, and total flavonoids increased significantly in mixoploid plants compared with tetraploid and diploid plants. Tetraploid plants had a higher amount of total proteins, total flavonoids, and starch in comparison with control plants. The results showed that polyploidization could increase the contents of tetrahydrocannabinol in mixoploid plants only, but tetraploid plants had lower amounts of this substance in comparison with diploids. Also, we found such changes in protein concentration in electrophoresis analysis. In overall, our study suggests that tetraploidization could not be useful to produce tetrahydrocannabinol for commercial use, and in this case, mixoploids are more suitable.

Effect of recombinant human IFNγ in the treatment of chronic pulmonary complications due to sulfur mustard intoxication.

Pulmonary problems are among the most common chronic complications of sulfur mustard (SM) intoxication and adversely affect patients' quality-of-life. The present trial investigated the impact of immunotherapy with interferon (IFN)-γ on quality-of-life, respiratory symptoms, and circulating immunologic and oxidative parameters in patients suffering from chronic SM-induced complications. Patients (n = 15) were administered IFNγ (100 µg) every other day for a period of 6 months. Assessment of quality-of-life [using St. George respiratory Questionnaire (SGRQ) and COPD Assessment Test (CAT) indices], the severity and frequency of respiratory symptoms, and serum levels of immunologic [including interleukin (IL)-2, IL-4, IL-6, IL-10, IFNγ, calcitonin gene related peptide (CGRP), matrix metallopeptidase (MMP)-9, and tumor necrosis factor (TNF)-α], oxidative stress [malondialdehyde (MDA) as well as total and reduced glutathione, and catalase and superoxide dismutase (SOD) activity], and fibrogenic [transforming growth factor (TGF)-ß] parameters were performed at baseline and at trial end. The results indicated that IFNγ therapy is associated with improvements in SGRQ (p < 0.001) and CAT (p < 0.001) scores, decreased severity of cough (p = 0.001), dyspnea (p < 0.001), and morning dyspnea (p < 0.001), reduced frequency of sputum production (p < 0.001) and hemoptysis (p < 0.001), and elevated FEV1 (p = 0.065). Serum levels of IL-4 (p < 0.001), IL-6 (p < 0.001), IL-10 (p < 0.001), CGRP (p < 0.001), MMP-9 (p = 0.001), TNFα (p < 0.001), TGFß (p < 0.001) and MDA (p = 0.001) were decreased while those of IL-2 (p < 0.001), IFNγ (p < 0.001), and both total (p = 0.005) and reduced glutathione (p = 0.061) increased by the end of the trial. It was concluded that IFNγ has favorable effects on the quality-of-life and alleviates respiratory symptoms in patients suffering from chronic SM-induced pulmonary complications. A modulation of cytokines and oxidative stress appears responsible for the clinical efficacy of IFNγ.